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关键细胞因子及其转录因子是糖醛酸(G2013)抑制多发性硬化免疫发病机制过程的靶点。

Pivotal cytokines and their transcription factors are the targets of guluronic acid (G2013) for inhibiting the immunopathogenesis process of multiple sclerosis.

机构信息

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Drug Dev Res. 2020 Jun;81(4):511-516. doi: 10.1002/ddr.21645. Epub 2020 Feb 26.

DOI:10.1002/ddr.21645
PMID:32103523
Abstract

The α-L-guluronic acid (G2013), is a novel immunosuppressive drug (PCT/EP2017/067920). One of the most popular ideas in designing drugs for multiple sclerosis (MS) is to restrict the main inflammation-related lymphocytes and cytokines. The foremost problems with conventional drugs are their side effects and low efficacy. In order to rectify these problems, we examined the effect of two doses of G2013 on the gene expression of IFN-γ, IL-17, IL-22, T-bet, RORC, and AHR, in MS patients PBMCs. RNA was extracted from peripheral blood mononuclear cell (PBMC) of 12 relapsing-remitting MS patients and 12 healthy volunteers and the effect of two doses of G2013 on the gene expression of IFN-γ, IL-17, IL-22, T-bet, RORC, and AHR, were assessed by real-time PCR. Overall, the results show that G2013 is able to significantly reduce the gene expression of IL-22, AHR, RORC, and T-bet. Collectively, G2013 might be considered and studied as a new drug of possible use to MS patients due to its immunosuppressive property on some of the main inflammatory cytokine and transcription factors.

摘要

α-L-古洛糖醛酸(G2013)是一种新型免疫抑制剂(PCT/EP2017/067920)。在多发性硬化症(MS)药物设计中,最流行的想法之一是限制主要的炎症相关淋巴细胞和细胞因子。传统药物的首要问题是它们的副作用和低疗效。为了纠正这些问题,我们研究了两种剂量的 G2013 对 MS 患者 PBMC 中 IFN-γ、IL-17、IL-22、T-bet、RORC 和 AHR 基因表达的影响。从 12 例复发缓解型 MS 患者和 12 例健康志愿者的外周血单个核细胞(PBMC)中提取 RNA,并通过实时 PCR 评估两种剂量的 G2013 对 IFN-γ、IL-17、IL-22、T-bet、RORC 和 AHR 基因表达的影响。总的来说,结果表明 G2013 能够显著降低 IL-22、AHR、RORC 和 T-bet 的基因表达。总之,由于 G2013 对一些主要炎症细胞因子和转录因子具有免疫抑制作用,因此可以考虑将其作为一种新的药物,用于 MS 患者。

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